Influence of maternal MTHFR A1298C polymorphism on the risk in offspring of schizophrenia

Several lines of evidence have suggested that two functional methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, C677T and A1298C, may be implicated in the etiology of schizophrenia. We examined these MTHFR polymorphisms in 111 families, composed of a patient and their parents, as well as 143 mothers of patients with schizophrenia and 235 age-matched mothers who had healthy children. The maternal MTHFR 1298C allele was associated with a significantly increased risk of schizophrenia (OR = 1.63, 95%CI: 1.11-2.39, P = 0.01). The haplotype analysis showed a weak association for the 1298C-677C haplotype (OR = 1.54, 95%CI = 1.03-2.29, P = 0.04). Analysis of Transmission Disequilibrium Test (TDT) showed no preferential transmission of 1298C and 677T alleles from parents to probands (P = 0.64 and P = 0.71, respectively). Our results suggest that deficient MTHFR enzyme activity in pregnant women, related to the A1298C variant, is associated with a higher risk of having offspring affected with schizophrenia. Given the low sample size in this study, the present results seem tentative and need further studies to replicate.